The connective tissue of the respiratory tree and of the interstitium of lung alveoli is of fundamental importance in the maintenance of lung structure and respiratory function. Although considerable information is available on collagen and elastin of lung connective tissue, very little is known about lung proteoglycans. This research will explore the nature of proteoglycans in the lung and will study their potential in biologic function. Efforts will be made to improve methods for isolation of proteoglycans using chemical and enzymatic techniques, and glycosaminoglycans and core proteins of the proteoglycans will be characterized. Whether the lung proteoglycans form aggregates like those from cartilage and what specific interactions of proteoglycans occur with collagen and elastin will be investigated. Interactions of proteoglycans with fibrous structures may be the important mechanism that produces and insoluble matrix. This matrix may function to protect from and to exclude potentially destructive molecules, such as proteases. Comparative studies on various species of animals will be conducted to learn whether any correlation exists between proteoglycan composition of the lung and species susceptibility to respiratory diseases. The composition of proteoglycans of lung at various stages of development will also be studied to provide information on the normal pattern of development of these macromolecules. As a model of human disease, experimental emphysema will be studied. The primary objective of the research program is to define more precisely the chemistry and function of proteoglycans in normal lung and the role these compounds play in the pathogenesis of a major lung disease, emphysema.